The phenomena of signal transduction is central to a myriad of critical functions in the molecular and cellular biology of almost all cells and organisms. Nowhere is this more evident than in the area of growth regulation. Increasing evidence has placed changes in and/or alterations of functions of important growth regulatory signaling pathways at the center of the pathogenesis of a number of human cancers. This program project will be a coordinated research effort directed at a number of candidate changes which are believed to play a role in some malignancies. The expertise and experience brought to bear in this research will cover a number of the important areas of signaling in oncogenesis including signaling through and blockade of type I receptor tyrosine kinases, alterations in the regulation of critical components of the PI3 kinase pathway, changes in the intracellular signaling through ras/mek/erk pathway, modulation of signals in the androgen response pathway and signaling with results in changes in important structural proteins involved in the transition from normal to malignant cells. This research is not designed to cover all areas of signal transduction and oncogenesis, but rather will capitalize on the expertise of project leaders and laboratories involved in the above mentioned areas to synergize overlapping research efforts in this important area of cancer biology. We feel the likelihood of important findings in both basic and translational research results from these efforts is high.